Glutathione-dependent inhibition of lipid peroxidation by a soluble, heat-labile factor in animal tissues.

A glutathione-dependent, cytosolic factor (previously thought to be glutathione peroxidase), inhibits lipid peroxidation in both microsomal and mitochondrial membranes. Studies in this laboratory had shown that the inhibition was due to prevention of peroxidative attack on the polyunsaturated fatty acids in the membrane lipids even under conditions that would otherwise promote rapid lipid peroxidation. A glutathione-dependent factor is also present in rat liver cytosol which can utilize peroxides of both free fatty acid salts in solution and free fatty acids in micellar suspension as substrates. It does not, however, utilize peroxidized lipids of microsomal and mitochondrial membranes as substrates. Whether or not this is the same factor which inhibits lipid peroxidation is not known with certainty, but current information indicates that they are not the same. Data presented in this report support the conclusion that neither glutathione peroxidase nor glutathione S-transferase activities appear to be responsible for the inhibition of lipid peroxidation in biological membranes. After partial purification of active preparations of both of these peroxidases, it was observed that neither preparation inhibited lipid peroxidation. The results of this study further support the conclusion that the glutathione-dependent cytosolic factor which inhibits lipid peroxidation in biological membranes does so by preventing the peroxidation rather than by reducing lipid peroxides.